A. Inorganic Oxide-Based Chromatographic Supports
Currently known inorganic chromatography supports comprising particulate silica (SiO.sub.2) or alumina (Al.sub.2 O.sub.3) are stable over pH ranges of about 1-8 and 3-12, respectively. The solubilization of SiO.sub.2 and Al.sub.2 O.sub.3 at pHs outside of these ranges results in the deterioration of these supports, and in contamination of the resultant chromatographed and separated products with silicon- or aluminum-containing species. Methods of improving the alkaline stability of particulate SiO.sub.2 by cladding the surface with a more base-stable metal oxide such as zirconium oxide (ZrO.sub.2) have been disclosed in U.S. Pat. Nos. 4,648,975 and 4,600,646. This cladding is disclosed to increase the upper pH limit at which these supports, also referred to as packings, can be used to 11 and 9.5, respectively. However, these packings still lack adequate stability to allow them to be sterilized and cleaned in, for example, 0.1N aqueous sodium hydroxide (NaOH, pH=13).
Use of porous spherical ZrO.sub.2 particles on a thin layer chromatography plate is disclosed in U.S. Pat. No. 4,138,336; a process for the preparation of porous ZrO.sub.2 microspheres is taught in U.S. Pat. No. 4,010,242; and chromatographic use of these particles is taught in U.S. Pat. No. 3,782,075. The microspheres are prepared by a process in which colloidal metal oxide particles are mixed with a polymerizable organic material and coacervated into spherical particles by initiating polymerization of the organic material. This is a time consuming, batch process which requires the addition of organic material which is later pyrolized and hence lost.
U.S. Pat. No. 3,862,908 discloses microspheres of urania and other metal oxides; however, these particles are fired to near full density, have reduced surface areas and therefore, would not be desirable for chromatographic uses.
U.S. Pat. No. 3,892,580 discloses a process for preparing porous bodies of ZrO.sub.2. This process requires the use of a binder to react with the oxide particles during preparation. This binder is subsequently decomposed by pyrolysis and therefore lost. The bodies produced by this process are not spherical, would pack unevenly, may cause increased column pressure, and are therefore not preferred for chromatographic uses.
U.S. Pat. No. 4,389,385 teaches the preparation of porous gels and ceramic materials by dispersing solid particles of an inorganic substance produced by a vapor phase condensation method in a liquid to form a sol. The sol contains colloidal particles which are aggregates of the primary particles. The sol is dried to produce a porous gel of greater than 70% by volume porosity.
Commonly-assigned U.S. patent application Ser. No. 07/420,150, filed Oct. 11, 1989, now U.S. Pat. No. 5,015,373, discloses a support material adapted for use as the stationary phase in liquid chromatography (LC), which comprises ZrO.sub.2 spherules preferably having a diameter of about 0.5-200 .mu., a surface area of about 1-200 m.sup.2 /g, and pore diameters of about 20-500 .ANG.. A preferred embodiment of the invention disclosed in the Ser. No. '150 application is directed to a chromatographic support material comprising ZrO.sub.2 spherules having a cross-linked polymeric coating thereon, wherein the coated spherules are hydrophobic, have a pore size from about 20-500 .ANG. and an average diameter of about 0.5-500.mu..